Nerve growth factor (NGF) is a polypeptide growth factor that is a member of the neutrophin family which includes brain-derived neurotrophic factor, neutrophin 3, and neutrophin 4/5. Two cell surface NGF receptors have been characterized on the basis of binding affinity and signal transduction properties, namely the p75 low affinity NGF receptor and p140 TrkA. NGF dimerizes in solution and interacts with two or three TrkA receptors to form a high affinity complex with a dissociation constant of 10-9 M. Isothermal titration calorimetric studies are currently in progress to determine an exact stoichiometry for the NGF-TrkA complex and resultant enthalpy and free energy of binding. Preliminary results indicate that one NGF dimer binds two TrkA receptors with an enthalpy of - 4.8 kcal/mol TrkA.